西罗莫司含量的分析测定移植患者的淋巴细胞。

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马斯里米,Rizk年代,Barbari,斯蒂芬,Kamel G,罗斯特M

西罗莫司含量的分析测定移植患者的淋巴细胞。

移植Proc。2007年5月,39 (4):1204 - 6。

PubMed ID

17524933 (在PubMed

]

文摘

他克莫司(TAC)和西罗莫司(SRL)绑定到同一个immunophilin FKBP12;然而,他们的作用机理是不同的。SRL抑制哺乳动物雷帕霉素靶(TOR),这是一种酶免疫功能的关键。TOR信号介导t细胞增殖抑制块通过阻止细胞循环发展G1 S期。此外,TOR抑制导致减少抗体生产通过阻断b细胞增殖和成熟抗体产生细胞。生存研究实验室的使用导致了拒绝集的数量减少。与其他免疫抑制剂,SRL可能导致剂量相关的副作用,其中最引人注目的高胆固醇血症,高脂血症、贫血和血小板减少。因此,治疗药物监测评估疗效和毒性已成为必要。SRL血液水平不与它的生物活性和影响伴随其他免疫抑制药物的使用。确定SRL的生物活性,我们开发了一个试验来确定水平的西罗莫司/淋巴细胞的移植患者。 The levels were correlated with lymphocyte count. METHODS: Whole blood samples from patients on SRL were collected in Ethylene Diamine Tetra-acetic acid (EDTA) vacutainer tubes. Immediately the lymphocytes from 2 mL of blood were separated using 1.5 mL of Ficoll gradient, by centrifugation for 30 minutes at 2500 RPM. The lymphocytes were washed three times with phosphate-bufferd saline and the pellet suspended in 150 microL of Middle East research institute (MERI) drug extraction solution (Beirut, Lebanon), which was then added to 300 microL of IMx solublizing reagent. The cytoplasmic SRL concentrations in lymphocytes were measured using kits supplied from Abbott diagnostics or by high-performance liquid tomography. A corresponding whole blood sample from each patient was used to measure blood levels. To determine the level per lymphocyte, the value obtained was divided by the number of lymphocytes and expressed as Pg/cell. A pharmacokinetic profile for both blood and lymphocytes was constructed for each patient using data corresponding to predose C(0), 1 hour (C(1)) and 2 hours (C(2)) after the dose. The lymphocyte enumeration for C(0), C(1), and C(2) was performed using the FACS Calibur Flow Cytometer from Becton Dickinson. The average dose was 2.86 +/- 1.27 mg/d with a C(0) = 8.05 +/- 4.24, C(1) = 21.9 +/- 8.9 ng/mL, and C(2) = 23 +/- 0.03 ng/mL. Although there was a significant correlation (P=.0975) between the dose and C(0), there was no correlation between the dose and C(0) level on the lymphocyte count P=.897. However, there was a strong correlation between SRL lymphocyte levels (pg/cell) and the lymphocyte count (r(2)=.6.06). The higher the concentration of the drug the lower the lymphocyte counts. The assay is sensitive to within 0.45 pg/cell, reproducible with a coefficient of variance (CV) of 6.4% within assay and 7.5% for intraassay.

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药物靶点

药物	目标	类	生物	药理作用	行动
他克莫司	Peptidyl-prolyl顺反异构酶FKBP1A	蛋白质	人类	是的	抑制剂	细节